Quick Answer

Direct randomized evidence comes from STEP 9, a 68-week trial in 407 adults with obesity and moderate knee osteoarthritis. Once-weekly Wegovy (semaglutide) 2.4 mg produced larger improvements than placebo in pain, body weight, and a general measure of physical function. On the 0-100 WOMAC pain scale, the average change was -41.7 points with semaglutide versus -27.5 points with placebo. Average body-weight change was -13.7% versus -3.2%. These figures come from the peer-reviewed New England Journal of Medicine report.

That is meaningful evidence for the population studied, but it does not prove that semaglutide regrows cartilage, works independently of weight loss, or that every GLP-1 medicine has the same effect. Semaglutide is also not FDA-approved specifically to treat osteoarthritis.

Key Points

The correct trial name is STEP 9, not “STEP OA.”
STEP 9 used semaglutide 2.4 mg once weekly plus lifestyle counseling for 68 weeks.
Its WOMAC pain results are point changes on a 0-100 scale, not percentage reductions.
The tested regimen corresponds to the traditional Wegovy weight-management dose, not an Ozempic regimen.
Pain and weight improved together; STEP 9 did not isolate a weight-independent drug effect on the joint.
Lilly's TRIUMPH-4 announcement is encouraging, but it is sponsor-reported topline evidence pending detailed peer review.
Retatrutide activates three receptors, so its results cannot confirm a GLP-1 class effect.

Why Weight and Knee OA Are Connected

Knee osteoarthritis is not simply “wear and tear.” Joint structure, previous injury, muscle strength, alignment, age, inflammation, and metabolic health can all matter. For people carrying excess body weight, mechanical load is one important and modifiable contributor.

A frequently quoted estimate comes from a gait-analysis study in older adults with overweight or obesity and knee OA. Researchers found that each pound of body weight lost was associated with roughly 4 pounds less knee-joint load per step. That is a biomechanical estimate during walking—not a promise that one pound of weight loss produces a fixed amount of pain relief. Read the primary study on PubMed.

Weight management can therefore be part of OA care, but it is not the whole plan. Exercise, physical therapy, pain treatment, and decisions about injections or surgery remain individualized.

STEP 9: The Main Semaglutide Trial

The pivotal study was STEP 9, funded by Novo Nordisk and published online on October 30, 2024. It was a double-blind, randomized, placebo-controlled phase 3 trial conducted at 61 sites in 11 countries. The trial registration is NCT05064735, and the full results were published in the New England Journal of Medicine.

Who was studied?

The trial enrolled 407 adults who had:

BMI of 30 or higher
A clinical and radiologic diagnosis of moderate knee osteoarthritis
At least moderate knee pain
No diabetes

Participants' mean age was 56, mean BMI was 40.3, and 81.6% were women. Those details matter: the findings should not automatically be generalized to people at lower weights, people with diabetes, or every OA phenotype.

What treatment was tested?

Participants were assigned in a 2:1 ratio to:

Semaglutide 2.4 mg by weekly injection, or
Placebo injection

Both groups also received counseling on physical activity and a reduced-calorie diet. The trial lasted 68 weeks.

What did STEP 9 find?

Outcome at week 68	Semaglutide 2.4 mg	Placebo	How to read it
Body-weight change	-13.7%	-3.2%	Percent change from baseline
WOMAC pain change	-41.7 points	-27.5 points	0-100 scale; lower is better
SF-36 physical-function change	+12.0 points	+6.5 points	0-100 scale; higher is better

All three between-group comparisons were statistically significant in the published report. The placebo group improved too, which can reflect lifestyle counseling, trial participation, symptom fluctuation, and placebo/context effects.

The pain numbers are easy to misstate. A drop of 41.7 on the normalized WOMAC scale is a 41.7-point change, not “41.7% pain reduction.” STEP 9's co-primary endpoints were percentage change in body weight and point change in WOMAC pain.

Safety and discontinuation

Serious adverse events occurred at similar rates in the two groups. Adverse events led to permanent treatment discontinuation in 6.7% of semaglutide participants and 3.0% of placebo participants; gastrointestinal disorders were the most common reason in the semaglutide group. This article cannot determine whether the medication is appropriate for a particular reader.

Wegovy-Dose Semaglutide Is Not the Same as Saying “Ozempic”

Wegovy and Ozempic contain the same active molecule, semaglutide, but they are separate products with different FDA labeling and dosing.

STEP 9 used 2.4 mg once weekly, the traditional maintenance dose associated with injectable Wegovy for weight management. The manufacturer-hosted Wegovy prescribing information describes the labeled weight-management regimen.

Ozempic is labeled for people with type 2 diabetes and related risk reduction, with injectable doses up to 2 mg weekly in its FDA prescribing information. STEP 9 excluded people with diabetes and did not test an Ozempic-labeled regimen. It is accurate to say the trial studied semaglutide; it is inaccurate to describe it as an “Ozempic knee arthritis trial.”

Did Semaglutide Work Beyond Weight Loss?

STEP 9 shows that semaglutide improved weight and knee symptoms at the same time. It does not answer exactly why pain improved.

Several explanations are plausible:

Mechanical unloading: less body weight can reduce knee forces during walking.
Better mobility: losing weight may make activity easier, which can improve strength and function.
Systemic metabolic changes: semaglutide and weight loss can change inflammatory and metabolic markers.
Possible direct joint effects: laboratory and animal work has proposed effects in cartilage and other joint tissues.

The key word is possible. STEP 9 was not designed to separate these pathways. It did not include a comparison group that achieved identical weight loss without semaglutide, and it did not establish cartilage regeneration.

A 2026 experimental report combined mouse work, cell experiments, and a small proof-of-concept clinical component and proposed a weight-independent metabolic pathway. That work is hypothesis-generating, not proof that routine semaglutide treatment regrows human cartilage. See the study record on PubMed.

Why This Is Not Yet a Proven Class Effect

Evidence from one drug should not automatically be assigned to every GLP-1 medicine. A randomized trial of liraglutide after diet-induced weight loss found additional weight loss but no significant difference in knee pain versus placebo over 52 weeks. The design and population differed from STEP 9, so this is not a head-to-head contradiction, but it shows why class-wide claims are premature. Read the liraglutide trial abstract.

There is also no dedicated, published knee-OA outcomes trial establishing that tirzepatide produces the same pain effect as STEP 9. Greater average weight loss in another setting does not by itself prove greater OA pain relief.

TRIUMPH-4: Promising, but Sponsor-Reported Topline Evidence

TRIUMPH-4 tested retatrutide in adults with overweight or obesity and knee osteoarthritis. Retatrutide is not a GLP-1-only drug: it activates GIP, GLP-1, and glucagon receptors.

According to Lilly's December 2025 news release, the phase 3 trial randomized 445 participants to retatrutide 9 mg, retatrutide 12 mg, or placebo for 68 weeks. In the sponsor's efficacy-estimand analysis:

Outcome	Retatrutide 9 mg	Retatrutide 12 mg	Placebo
Body-weight change	-26.4%	-28.7%	-2.1%
WOMAC pain change on 0-10 scale	-4.5 points	-4.4 points	-2.4 points
WOMAC physical-function change on 0-10 scale	-4.1 points	-4.2 points	-2.1 points

The percentages Lilly attached to WOMAC change were calculated in a post-hoc analysis, and some responder analyses were not controlled for multiple comparisons. The sponsor said detailed results would be presented at a medical meeting and published in a peer-reviewed journal. The ClinicalTrials.gov record listed the study as complete but did not contain posted results when this article was updated.

That evidence should be described as positive sponsor topline results, not as independently peer-reviewed confirmation. Because retatrutide works at three receptor systems and produced large weight loss, TRIUMPH-4 also cannot establish that knee-pain improvement is a GLP-1 class effect or a direct GLP-1 action in the joint.

Retatrutide remains investigational and is not FDA-approved. See our retatrutide guide for a broader overview.

What the Evidence Does—and Does Not—Support

Supported by current trial evidence

Semaglutide 2.4 mg improved pain and body weight more than placebo over 68 weeks in adults with obesity and moderate knee OA.
A general physical-function score also improved more with semaglutide.
Substantial weight loss can reduce mechanical knee load.
Sponsor-reported TRIUMPH-4 results show pain, function, and weight improvements with investigational retatrutide versus placebo.

Not established

That semaglutide regrows cartilage or reverses structural OA damage
That STEP 9's pain benefit was independent of weight loss
That GLP-1 drugs treat OA in people without obesity
That all GLP-1 or incretin medicines share the same OA effect
That Ozempic dosing produces the STEP 9 result
That retatrutide is safe and effective for routine care before regulatory review and detailed publication

How This Fits With Standard Knee OA Care

A medication used for weight management does not replace knee-focused care. A clinician may consider several elements depending on symptoms, health history, and imaging:

Exercise and progressive strengthening
Physical therapy
Weight management when relevant
Topical or oral pain medicines when appropriate
Injections for selected patients
Assistive devices or bracing
Orthopedic evaluation when symptoms remain severe

Our exercise guide for people taking GLP-1 medicines includes ways to build activity gradually. If pain is new or started after beginning treatment, see our separate guide to GLP-1s and joint pain.

Semaglutide has contraindications, warnings, and common gastrointestinal adverse effects. Rapid weight loss can also affect lean mass, so nutrition and resistance exercise deserve attention. For related context, read our guide to GLP-1s and bone health.

Questions to Ask a Clinician

If you have obesity and knee OA and are already discussing weight-management treatment, useful questions include:

Do I meet the labeled criteria for this medication independent of my knee pain?
How do my diabetes status, gallbladder history, eye health, medications, and other conditions affect the choice?
What knee-specific treatment and exercise plan should continue alongside weight management?
How will we track pain, function, muscle strength, and adverse effects?
What result would justify continuing, changing, or stopping treatment?

Do not switch between Wegovy and Ozempic, change a dose, or obtain investigational retatrutide based on an article or social-media claim.

The Bottom Line

STEP 9 provides solid evidence that semaglutide 2.4 mg weekly can reduce pain and improve physical function in adults with obesity and moderate knee osteoarthritis, while also producing substantial weight loss. The accurate headline is important: this was Wegovy-dose semaglutide, pain changed by points on a 0-100 WOMAC scale, and the trial did not prove cartilage regrowth or a weight-independent joint effect.

TRIUMPH-4 adds encouraging evidence for retatrutide, but the available results are sponsor-reported topline findings, and retatrutide's three-receptor mechanism cannot confirm a GLP-1 class effect. These medicines may become an important part of care for some people who already meet weight-management indications, but they are not substitutes for a complete osteoarthritis plan.

Disclaimer: This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before starting, stopping, or changing a medication or treatment plan. Semaglutide is not FDA-approved specifically for osteoarthritis, and retatrutide is investigational and not FDA-approved.

GLP-1s and Knee Osteoarthritis: What STEP 9 Actually Found